Development Of Opportunistic Infections Research Articles

The whole-genome molecular epidemiology of sequential isolates of Acinetobacter baumannii colonizing the rectum of patients in an adult intensive care unit of a tertiary hospital.

Acinetobacter baumannii is a nosocomial multidrug-resistant pathogen that specifically colonizes and infects patients in intensive care units (ICUs). Genome plasticity of A. baumannii may contribute to the rapid development of A. baumannii resistance during patient treatment. There is little clarity on the dynamics of colonization of A. baumannii in humans. We studied 269 serial isolates of A. baumannii colonizing the rectum of 32 adult patients in an ICU; 5 to 16 isolates were obtained from each patient over a period of weeks to months. The isolates were sequenced using the Illumina platform. Multi-locus sequence typing revealed genetic diversity with 13 sequence types (STs); the dominant ST2 accounted for 202 of the 269 isolates and was isolated from each patient. A core genome comparison of isolates was used to elucidate a detailed understanding of the relationship among isolates within an ST and the genomic relationship among STs. One to three STs were observed in the isolates from each patient. Instances of unchanged colonization, sequential lineage colonization, and colonization with multiple lineages of A. baumannii were seen. The number of resistance genes carried by the isolates varied from 2 to 17. The predominant genes corresponded to those encoding resistance to β-lactam and aminoglycoside antibiotics. Generally, there was a strong correlation between ST and a particular antimicrobial resistance gene profile. This study makes an important baseline contribution to information that will help us understand the role of A. baumannii colonization in the development of opportunistic infections in ICU patients. IMPORTANCE Acinetobacter baumannii is a multidrug-resistant nosocomial pathogen that colonizes and infects debilitated patients in the ICU. There is very little information on the genomic characteristics of colonizing strains. This information is important to understand the evolution of lineages of A. baumannii that develop resistance while patients receive antibiotic treatment in the ICU. Our study demonstrated different patterns of colonization of the rectum of ICU patients with different STs of A. baumannii while one ST colonized all patients. Some STs carried more antibiotic resistance genes compared to others. However, there was a correlation between ST and a particular resistance gene profile. Our results further elucidate the dynamics of enteric colonization of this opportunistic pathogen.

Bacterial, Fungal and Viral Infections in Patients with Hematological Malignancies: Investigation of CMV Reactivation as a Risk Factor

Reactivation of latent viruses such as human cytomegalovirus (CMV), as well as opportunistic infections associated with bacterial and fungal agents, cause serious clinical consequences in patients with hematological malignancies, which are characterized by both immunosuppressive drug use and functional and numerical disorders of immune system cells. In this study, it was aimed to investigate the association between CMV reactivation and the frequency of various simultaneous infections in adult patients with hematological malignancies. All CMV-DNA test results reported in the medical microbiology laboratory between November 2016 and February 2022 were retrospectively reviewed and the study group consisting of 270 adult patients with hematological malignancies was created. CMV-DNA follow-up results and clinical evaluations of these patients were examined and cases with CMV reactivation were determined. In the final stage, the possible association between CMV reactivation and the frequency of other infections identified by microbiological examination of patients' samples and radiological and clinical evaluations was investigated. Of 270 adult patients with hematological malignancies in the study group, 175 (64.8%) were male and 95 (35.2%) were female, and the mean age of the patients was 50.98 (±17.6). It was determined that 35.9% (97/270) of the patients had CMV reactivation during the follow-up period. The presence of 139 bacterial agents in 99 patients, 63 viral agents in 58 patients, and 56 fungal agents in 50 patients were determined. Bacterial infections were as follows according to the systems; 108 bacteremia (most frequently detected agent Escherichia coli; n=31, 28.7%), 21 urinary tract infections (most common cause E. coli; n=13, 61.9%), and 10 other bacterial infections. Fungal infections were as follows according to the systems; 36 respiratory tract infections (most common Aspergillus spp.; n=23, 63.9%), 6 fungemia (all Candida spp.), 14 other fungal infections (Candida spp.; n=11, and mucormycosis; n= 3). Viral infections were as follows, in order of frequency; hepatitis B (anti-HBc IgG seropositivity in 30 patients), COVID-19 (Coronavirus Disease-2019) in 14 patients, herpes simplex virus in 11 patients, herpes zoster in four patients, BK virus in three patients, and parvovirus B19 in one patient. CMV reactivation rates were found to be significantly higher in patients with fungal pneumonia, non-CMV viral reactivation, and bacterial bloodstream infection, p=0.046, p=0.003, and p=0.038, respectively. In the literature, CMV reactivation, risk factors associated with reactivation, and adverse clinical outcomes of CMV reactivation in patients with hematological malignancies have been investigated from many different aspects. However, additional pressures of CMV on the immune system and its negative effects on innate and adaptive immune responses and possible contributions of this situation to the development of other infections have not yet been studied in detail. We think that determining the possible effects of CMV reactivation on the development of opportunistic infections by comprehensive prospective studies may change antimicrobial therapy strategies in the management of CMV infections.

Prevalence and determinants of opportunistic infections among HIV-infected adults receiving antiretroviral therapy in Ethiopia: A systematic review and meta-analysis.

Reliable data on the burden of opportunistic infections (OIs) after the initiation of antiretroviral therapy (ART) is critical for planning health services and reducing OI-related morbidity and mortality. Nevertheless, there has been no nationally representative information on the prevalence of OIs in our country. Therefore, we have undertaken this comprehensive systematic review and meta-analysis to estimate the pooled prevalence, and identify factors associated with the development of OIs in Human Immunodeficiency Virus (HIV)-infected adults receiving ART in Ethiopia. Articles were searched in international electronic databases. A standardized Microsoft Excel spreadsheet and STATA software version 16 were used for data extraction and analysis, respectively. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist was used to write this report. The random-effect meta-analysis model was used to estimate the pooled effect. The statistical heterogeneity of the meta-analysis was checked. Subgroup and sensitivity analyses were also performed. Publication bias was examined in funnel plots and the nonparametric rank correlation test of Begg and the regression-based test of Egger. Association was expressed through a pooled odds ratio (OR) with a 95% Confidence Interval (CI). A total of 12 studies with 6,163 study participants were included. The pooled prevalence of OIs was 43.97% [95% CI (38.59, 49.34)]. Poor adherence to ART [OR, 5.90, 95% CI (3.05, 11.40)], under nutrition [OR, 3.70, 95% CI (2.01, 6.80)], CD4 T lymphocyte count <200 cells /μL [OR, 3.23 95% CI (2.06, 5.07)], and advanced World Health Organization (WHO) HIV clinical stages [OR, 4.84 95% CI (1.83, 12.82)] were determinants of OIs. The pooled prevalence of OIs among adults taking ART is high. Poor adherence to ART, under nutrition, a CD4 T lymphocyte count <200 cells /μL, and advanced WHO HIV clinical stages were factors associated with the development of OIs.

TOXOPLASMOSIS OF THE CENTRAL NERVOUS SYSTEM IN HIV PATIENTS

Currently HIV infection in Kazakhstan is mainly spread among population groups with risk taking behavior (injection drug users - IDUs, sex workers - SWs). The lesions and fatalities in patients with HIV infection are mainly caused by complications, i.e. the development of opportunistic infections and secondary diseases. Timely diagnosis of these conditions determines the success of treatment and life expectancy of patients. Among superinfections the following ones take the lead: mycoses (pneumocystosis, candidiasis, cryptococcosis, coccidioidosis), diseases caused by a group of herpes viruses (herpes simplex, herpes zoster, cytomegalovirus infection, Epstein-Barr virus infection, Kaposi's sarcoma), bacterial infection (tuberculosis, atypical mycobacteriosis, salmonellosis), protozoosis (toxoplasmosis, cryptosporidiosis). Multi-infections are common as well. Opportunistic infections are insidious in humans and take the form of endogenous infections; they as well are activated with the development of clinical manifestations along with formation of immunodeficiency and, accordingly, cause severe and even fatal diseases.

Clinical and immunological characteristics of opportunistic infections in children with the natural course of HIV infection, taking into account the route of infection

The purpose of the study is to improve the diagnosis and prognosis of opportunistic infections in children infected with HIV by vertical and parenteral routes, taking into account the dynamics of clinical and immunological parameters.Research methods. Clinical and laboratory examinations were carried out in 192 children infected with HIV by the vertical route (91; group I), parenteral route in infancy (44; group II) and over the age of one year (57; group III).Research results. In group I, a rapid development of immunosuppression was observed: mild immunodeficiency was diagnosed at the age of Me 4 (IQI 2—10) months, advanced immunodeficiency — Me 11 ( IQI 6—24.5) months, severe immunodeficiency — Me 23 ( IQI 11— 56) months. Clinical manifestation of opportunistic infections occurred in the first three years of life with a relatively high content of CD4-lymphocytes. Localized bacterial infections (Me 27,5; IQI 21,9–34,1/100 MYO), candidiasis (Me 14,1; IQI 10,2—18,9 / 100 MYO) and generalized infections (Me 5,2; IQI 2,9—8,5 / 100 MYO) had the highest relative incidence rate. In group II, there was a slower progression of immunosuppression (within one to seven years), the addition of opportunistic infections with a lower content of CD4-lymphocytes, in terms of one to nine years, a high relative incidence of herpes simplex infection (Me 12,9; IQI 7,8—14,9 / 100 MYO), herpes zoster (Me 3; IQI 1,5—5,4 / 100 MYO) and pneumocystosis (Me 3,8; IQI 2,1—6,4 / 100 MYO). In group III, there was a slow progression of immunosuppression (within one to eight years), the development of opportunistic infections with a low content of CD4-lymphocytes, in terms of two to ten years, a rarer manifestation of most diseases.Conclusion. These patterns should be taken into account when planning diagnostic, therapeutic and preventive measures in children with HIV infection, taking into account the path and age at the time of infection.

Experiences of Antiretroviral Therapy Initiation Among HIV-Positive Adults in Ethiopia: A Descriptive Phenomenological Design.

PurposeThe aim of the study was to explore and describe the lived experiences of HIV-positive adults on antiretroviral therapy (ART) initiation in West Shoa Zone, Ethiopia.Materials and MethodsA descriptive phenomenological design was utilized in the study to gain insight into participants’ lived experiences regarding ART initiation in West Shoa Zone, Ethiopia. Data were collected through semi-structured in-depth interviews and analyzed by means of thematic analysis.ResultsThe study found that spousal influence, denial of status, inconsistent ART initiation protocol, poverty, fear of side effects, religion and shortages of staff were factors that caused delayed ART initiation. A low CD4 count, the development of opportunistic infections and the prevention of future illness were factors that promoted ART initiation.ConclusionThis study provides an overview of experiences of adults living with HIV regarding ART initiation. The study emphasizes the need to improve adequate provision of resources to address issues related to finance, human capital, guidelines and inequity to enhance early ART initiation among HIV-positive adults in West Shoa Zone. The study findings have implications for policy implementation, ART service delivery, and the enhancement of prompt ART initiation in the study settings.

Determination of the direction of action of «EM® PROBIOTIC FOR BEES» against bee dysbacteriosis pathogens in vitro

In many countries around the world, massive declines in bee colonies have been reported as a consequence of the multifactorial effects of exogenous and endogenous factors. The development of opportunistic infections in bees is due to an imbalance of opportunistic pathogenic microflora that colonise the midgut of insects. The problem of dysbacteriosis in various animal species, including bees, is of interest to veterinarians. Therefore, the search for new remedies alternative to antibiotics is a high priority in beekeeping. Probiotic preparations have been proposed as new and safe medicines for the treatment and prevention of dysbacteriosis in human and veterinary medicine. Probiotics are products containing live micro-organisms that are able, in a certain dosage, to influence the macro-organism effectively. The application of such therapeutic additives to insects is preceded by their preliminary in vitro testing. Therefore, the main aim o the study was to determine the direction of action (bacteriostatic, bactericidal, antagonistic) of «EM® PROBIOTIC FOR BEES», diluted with sugar syrup solution and water in different concentrations, against Klebsiella pneumoniae, Klebsiella (Enterobacter) aerogenes bacteria and on mixed microbialas sociation in vitro. An in vitro experiment on the above probiotic agent was carried by diffusion in agar wells (well method) and a modified KirbyBauer method for the beekeeping industry (disk diffusion method). Bacteriostatic, bactericidal and antagonistic effects were determined visually and by measuring diameter of the are aaround the discs and wells. The bacteriostatic effect of probiotic microorganisms against enterobacteriaceae of Klebsiella pneumoniae species was recorded to be maintained at the same level when diluted with 50 % sugar syrup solution in concentrations from 0.5 % to 30 %. «EM® PROBIOTIC FOR BEES» diluted with water had pronounced antagonistic effect against Klebsiella pneumoniae bacteria by diffusion in agar wells method at concentrations of 0.5 % - 75,4±1,04 mm and 1% - 61,2±0,42 mm on the third day of the experiment. By diluting the probiotic with 50% sugar syrup solution, inhibition of the growth of Klebsiella (Enterobacter) aerogenes bacteria was observed in concentrations of up to 50%, ranging from 18,2±0,42 mm to 25,4±0,45 mm (disk diffusion method). Bactericidal effect of «EM® PROBIOTIC FOR BEES» diluted with water against mixed microbial association isolated from bee colonies with signs of intestinal disorders was observed at a concentration of 10% with a diameter of 18,6±0,57 mm by the disk diffusion method. Thus, «EM® PROBIOTIC FOR BEES» has antagonistic, bacteriostatic and bactericidal effects against enterobacteriaceae of bees Klebsiella pneumoniae, Klebsiella (Enterobacter) aerogenes species and agaist mixed microbial associations. The nature of the action of this probiotic depends on the solvent and its concentration, which in turn determines the direction and purpose of its application. Key words: beekeeping, dysbiosis, Klebsiella (Enterobacter) aerogenes, Klebsiella pneumoniae, bactericidal and bacteriostatic effects, antagonistic action.

Opportunistic Infections in Patients Receiving Daratumumab Regimens for Multiple Myeloma (MM)

BackgroundDaratumumab-based treatment regimens for MM have improved outcomes for both transplant-eligible and ineligible patients. As a result, patients are receiving longer exposure to this CD38 targeting monoclonal antibody. Adverse events (AE) including hypogammaglobulinemia, neutropenia, and lymphopenia have been reported in both clinical trials and retrospective studies, but with limited and contrasting data on the associated risk of developing infections. Furthermore, there remains a paucity of data on the risk of developing opportunistic infections in this growing patient population. The aim of this study is to assess the association between daratumumab-containing regimens and the development of opportunistic infections as reported to the Food and Drug Administration's Adverse Events Reporting System (FAERS), a pharmacovigilance monitoring database.Methods/MaterialsFAERS was queried for AE reports to evaluate the association of Cytomegalovirus reactivation (CMVr), Hepatitis B reactivation (HBVr), progressive multifocal leukoencephalopathy (PML), Herpes Zoster (HZ), Tuberculosis (TB), Pneumocystis Jirovecii (PJP), and Bronchopulmonary Aspergillosis (BA) with daratumumab-containing regimens from 2015-2021. The strength of an association between an infection reported with daratumumab in MM was compared with all events reported in MM treated patients, and the composite of all reported AE cases in FAERS. Signal disproportionality was calculated by using the reporting odds ratio (ROR), with the precision of the ROR determined by 95% confidence intervals (95% CI). Associated p-values were calculated by using chi-squared or Fisher's Exact test, with a p-value <0.05 considered statistically significant. Other reported variables concomitantly reported with daratumumab-treated patients were collected, including reported chemotherapy, >1 MM regimen, proteasome inhibitor (PI) use, or lenalidomide use.ResultsOut of the 12,393,747 AE cases reported to FAERS, there were 288,294 (2.3%) AE reported with MM patients, of which 7,152 (2.5%) were reported with daratumumab. There were 195 (2.7%) opportunistic infections reported with daratumumab, with a median age of 64 (42-89) years, and 64 (32.8%) were females. HZ (N=49, 25.1%) was the most common, followed by CMVr (N=43, 22.0%), PML (N=35, 17.9%), PJP (N=34, 17.4%), BA (N=16, 8.2%), HBVr (N=13, 6.7%), and TB (N=5, 2.5%). Neutropenia was reported in 29 (14.9%) of these patients, lymphopenia in 6 (3.1%), and hypogammaglobulinemia in 1 (0.51%) case. With comparison to all reported events in the FAERS database, a significant signal disproportionality was found with HZ (ROR 3.48 [95% CI 2.63, 4.61], p<0.0001), CMVr (ROR 33.31 [95% CI 24.61, 45.08], p<0.0001), PML (ROR 16.69 [95% CI 11.96, 23.31], p<0.0001), PJP (ROR 12.87 [95% CI 9.18, 18.05], p<0.0001), BA (ROR 9.82 [95% CI 6.01, 16.06], p<0.0001), and HBVr (ROR 9.35 [95% CI 5.42, 16.14], p<0.0001). When comparing reported infections with AE associated with MM patients in FAERS, HZ (ROR 1.59 [95% CI 1.19, 2.11], p=0.0015), CMVr (ROR 28.82 [95% CI 19.44, 42.72], p<0.0001), PML (ROR 13.04 [95% CI 8.89, 19.12], p=<0.0001), PJP (ROR 9.58 [95% CI 6.59, 13.96],p<0.0001), BA (ROR 11.46 [95% CI 6.56, 20.01], p<0.0001), HBVr (ROR 4.41 [95% CI 2.49, 7.83],p<0.0001), and TB (ROR 6.15 [95% CI 2.39, 15.78], p<0.0001) met statistical significance (Table 1). The proportion of concomitant medications reported with daratumumab is reported in Figure 1.ConclusionThis study suggests a significant association between daratumumab-based regimens and multiple opportunistic infections. Patients with known chronic viral infections or who are heavily pretreated should be monitored for these potential complications. FAERS data is beneficial in reporting associations between medications and AE but does not necessarily indicate causality. Further studies are needed to corroborate these findings. [Display omitted] DisclosuresGanguly: Kadmon: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Bristol Myer Squibb: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees.

Using atomic force microscopy to work with the cell surface of Candida albicans

Candida albicans is a yeast-like fungus that lives on human mucous membranes and skin and does not cause infections. However, it plays a role in the development of opportunistic infections in immunocompromised people. In this work, we would like to evaluate the possibility of studying the cell wall of C. albicans by atomic force microscopy, as well as compare the operating modes of the microscope and choose optimal one for working with the fungus. Atomic force microscopy is a powerful tool for evaluating surfaces, including the cell walls of biological objects. The microscope is capable of operating in different modes, but in this study we compared two of them: contact and semi-contact. These methods are the most popular for evaluating the surfaces of biological objects. Comparison of the modes was carried out on the C. albicans strain. The surface of the strain was scanned by atomic force microscopy, and the curves of the dependence of the sensor deviation from the distance to the object were recorded. Scanning and recording of curves were carried out in two modes of operation of the microscope: contact and semi-contact, as well as three sensors: soft, medium and hard.

Practical monitoring of the clinical efficacy of sinquanon in patients on antibiotic therapy

For more than seven decades, antibiotics and chemotherapeutics have been used successfully to treat and prevent infectious diseases, extensively changing the prognosis of severe infections and helping to improve quality of life. In the last two decades, the key role of the intestinal microbiota (IM) in basic vital functions such as digestion, protection against pathogens, and maintenance of immune and metabolic homeostasis has been recognized. Antibiotics do not selectively attack pathogenic bacteria. They have an effect on the normal microflora and can lead to imbalance inside the body (dysbacteriosis) and the development of opportunistic infections. Taking a probiotic during antibiotic treatment is one of the approaches to prevent antibiotic-associated diarrhea and other adverse effects of antibiotics when their use is necessary. In the present practical monitoring we want to share our results from the application of Sinquanon® to neutralize the negative effect of antibiotic treatment on the microbiome.

Expanding spectrum of opportunistic infections associated with dimethyl fumarate

Background: Only progressive multifocal leukoencephalopathy (PML) is currently described in the dimethyl fumarate (DMF) prescribing information. Objectives: To describe opportunistic infections (OIs), other than PML, reported in association with DMF. Methods: The FDA Adverse Event Reporting System (FAERS) and medical literature were searched. Results: We retrieved 34 cases of serious OIs with a causal association with DMF, including 11 central nervous system (CNS) infections and 23 extra-CNS infections. Six OIs occurred with normal circulating absolute lymphocyte counts. The median latency from DMF initiation was 13 months and was variable. Conclusion: DMF is associated with the development of OIs that require invasive diagnostic and/or therapeutic procedures. Patients should be monitored for OIs when treated with DMF regardless of circulating absolute lymphocyte counts.

Antiviral activity of extracts of basidiomycetes and humic compounds substances against Human Immunodeficiency Virus (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus 1) and Herpes Simplex Virus (Herpesviridae: Simplexvirus: Human alphaherpesvirus 1)

One of the most urgent problem of modern medicine is the fight against the disease caused bythe Human Immunodeficiency Virus (HIV) - HIV infection. The chemical compounds have improved the situationfor infected people, but they are toxic, disrupt the metabolism and cannot eliminate the integrated virus from thebody. The emergence of resistant HIV strains makes these treatments ineffective. Often, the death of HIV-infectedpeople occurs as a result of the development of opportunistic infections caused by viruses of the Herpesviridaefamily. Therefore, the search for new therapeutic and preventive drugs that are less toxic and active against severalviruses at the same time is relevant. Basidiomycetes, higher fungi, are a source of medicinal compounds that haveantimicrobial properties, as well as antiviral ones. Humic compounds (HS) of various nature also have antiviralactivity.The aim of the study was to obtain nontoxic compounds from the basidiomycete Inonotus obliquus and humiccompounds from brown coals and to test their activity against viruses that are pathogenic to humans: HIV andHerpes Simplex Virus (HSV). The antiviral activity of melanin extracts obtained from the culture of the chaga fungusInonotus obliquus and HS from the brown coal of the Kansko-Achinsk Deposit was studied using a model of MT-4lymphoblastoid cells infected with HIV type 1 (HIV-1) strains and a monolayer culture of Vero cells infected withHSV type 1 (HSV-1) using virological and statistical research methods. It was found that all the studied compounds did not have a cytotoxic effect on cells at aconcentration of 100 mcg/ml. It was shown that extracts of basidiomycetes and HS have antiviral activity againstHIV-1 and HSV-1. EC50 (50%-effective concentration) for HIV-1 was 3.7-5.0 mcg/ml, selectivity index 28-35.Antiherpetic activity was detected at a dose of 50-100 mcg/ml. The antiviral effectiveness of melanin compoundswas established both in the «preventive» (2 hours before cell infection) and in the «therapeutic» regimen of drugadministration, both for HIV-1 and HSV-1. The presence of antiviral activity of melanin and HS in relation to theRNA-containing HIV-1 virus and DNA-containing HSV-1 virus in our study coincides with the results of a number ofauthors in relation to influenza viruses, herpes virus, HIV, hepatitis B virus, Coxsackievirus, smallpox vaccine virus,which suggests that the type of nucleic acid in the virus does not play a fundamental role in the antiviral action ofthese drugs. It is also clear that HS is effective against both enveloped and non-enveloped viruses. In general, it can be concluded that melanin and humic compounds are characterized by low toxicityin the presence of both virucidal and antiviral activity. This allows us to consider the studied compounds as thebasis for creating safe medicines that are effective against pathogens of various viral infections.

Mycobacteriosis treatment challenges in patients with HIV-infection

Over the past decade, in Russian Federation there has been a steady increase in the incidence of MAC-infection in patients with HIV (the growth of nosology over the past five years, on average, was 57% per year). This determines the interest in this problem, especially in terms of the high inefficiency of treatment for the disease, the long term and cost of treatment. The history of the study of Mycobacterium Avium Complex-infection (MAC) originates in the early eighties in the United States, when the prognosis for a patient with AIDS and mycobacteriosis was extremely poor: mortality within one year after the detection of pathogen reached 71%. The role of infection in the thanatogenesis of patients was, however, established only by the beginning of the nineties. The detection of macrolide activity against the pathogen significantly improved the prognosis for patients, especially in combination with highly active antiretroviral therapy. The widespread introduction of antiviral drugs into practice and the ability to achieve immune reconstitution prevented the development of opportunistic infections, but did not solve the remaining issues of the treatment of the MAC-infection. The main one is the treatment of patients with a clarithromycin-resistant pathogen. There is no consensus on the sensitivity of non-tuberculous mycobacteria to antibacterials.

Influence of Vitamin D Deficiency on the Development of Opportunistic Infection in People Living with HIV/AIDS (PWHAs)

Background It is known that vitamin D is associated with immune cell growth, and an association between vitamin D deficiency and development of chronic infections such as tuberculosis has been reported. However, there have been few studies concerning the association between vitamin D deficiency and opportunistic infection (OI) in people living with HIV/AIDS (PWHA). Method PWHAs who had vitamin D (25-OH vitamin D, 25OHD) test results from 2012 to 2017 were enrolled. All enrolled PWHAs were divided into a vitamin D-deficient group and non-deficient group according to the 25OHD cutoff set by ROC curve analysis. The rates of OIs were compared between the two groups. Results Among 440 enrolled PWHAs, 394 (89.5%) were male, 32 were ≥ 65 years (13.4%), 237 (53.9%) were ART-naïve, and 107 (24.3%) had CD4 + T cell < 200/L. Seventy-three cases of OIs occurred in 63 PWHAs (14.3%); the most common OI was tuberculosis (27, 6.1%) followed by pneumocystis pneumonia (PCP) (25, 5.7%), and Cytomegalovirus (CMV) diseases (10, 2.3%). In the ROC curve analysis, the AUC was 0.71 (95% CI 0.64- 0.79, P < 0.001) and the optimal cutoffs of 25OHD to predict OIs was 14 ng/mL. Overall OI development was significantly more prevalent in the vitamin D-deficiency group (aOR 3.05, 95% CI 1.43-6.48); tuberculosis (aOR 3.51, 95% CI 1.22-10.05) and CMV disease (aOR 10.13, 95% CI 1.11-92.03) were significantly associated with vitamin D deficiency, whereas PCP was not (aOR 1.32, 95% CI 0.44-3.98). Conclusion Stringent cutoffs of vitamin D deficiency (< 14 ng/mL) were well correlated with development of OIs in PWHAs. Vitamin D deficiency was associated with development of OIs, particularly tuberculosis and CMV infections.

Tacrolimus trough levels higher than 6 ng/mL might not be required after a year in stable kidney transplant recipients.

BackgroundLittle is known regarding optimal tacrolimus (TAC) trough levels after 1 year post-transplant in stable kidney transplant recipients (KTRs) who have not experienced renal or cardiovascular outcomes. This study aimed to investigate the effect of 1-year post-transplant TAC trough levels on long-term renal and cardiovascular outcomes and opportunistic infections in stable KTRs.MethodsKTRs receiving TAC with mycophenolate-based immunosuppression who did not experience renal or cardiovascular outcomes within 1 year post-transplant were enrolled from a multicenter observational cohort study. Renal outcome was defined as a composite of biopsy-proven acute rejection, interstitial fibrosis and tubular atrophy, and death-censored graft loss. Cardiovascular outcome was defined as a composite of de novo cardiomegaly, left ventricular hypertrophy, and cardiovascular events. Opportunistic infections were defined as the occurrence of BK virus or cytomegalovirus infections.ResultsA total of 603 eligible KTRs were divided into the low-level TAC (LL-TAC) and high-level TAC (HL-TAC) groups based on a median TAC level of 5.9 ng/mL (range 1.3–14.3) at 1 year post-transplant. The HL-TAC group had significantly higher TAC trough levels at 2, 3, 4, and 5 years compared with the levels of the LL-TAC group. During the mean follow-up of 63.7 ± 13.0 months, there were 121 renal outcomes and 224 cardiovascular outcomes. In multivariate Cox regression analysis, LL-TAC and HL-TAC were not independent risk factors for renal and cardiovascular outcomes, respectively. No significant differences in the development of opportunistic infections and de novo donor-specific anti-human leukocyte antigen antibodies and renal allograft function were observed between the two groups.ConclusionsTAC trough levels after 1 year post-transplant remained at a similar level until the fifth year after kidney transplantation and were not directly associated with long-term outcomes in stable Korean KTRs who did not experience renal or cardiovascular outcomes. Therefore, in Asian KTRs with a stable clinical course, TAC trough levels higher than approximately 6 ng/mL might not be required after a year of kidney transplantation.

Prevalence And Predictors Of Opportunistic Infections Among HIV Positive Adults On Antiretroviral Therapy (On-ART) Versus Pre-ART In Addis Ababa, Ethiopia: A Comparative Cross-Sectional Study.

PurposeData comparing the burden of the opportunistic infections among the Pre-ART and On-ART HIV-infected patients in Ethiopia are scarce. Therefore, this study aimed to compare the prevalence and predictors of opportunistic infections in Pre-ART and On-ART HIV-infected patients.MethodsA comparative cross-sectional study was conducted among adult patients infected with HIV and who were on Pre-ART or On-ART and followed up from 2012 to 2016 in Zewditu Memorial Hospital, Addis Ababa. Those patients who were infected with HIV, but not eligible for ART were categorized under Pre-ART follow-up (n=192) and those patients who started taking ART were categorized under the On-ART follow-up group (n=192). Patients were included in the study by using simple random sampling technique from the list of the patients registered in the ART follow-up database. The presence of opportunistic infections along with clinical findings and baseline laboratory data was extracted from the ART follow-up database and the medical records of the patients using a standardized checklist. Factors associated with the development of opportunistic infections were analyzed using multi-variable binary logistic regression analysis.ResultsThe overall prevalence of opportunistic infections was found to be 33.6% (95% CI; 28.9–38.5). The prevalence of opportunistic infections among the Pre-ART group (38%) was higher than On-ART group (29.2%) (P-value = 0.04). Pulmonary tuberculosis was the most common opportunistic infection observed in both Pre-ART and On-ART groups. Being in the WHO clinical Stage III (AOR = 2.1; 95% CI 1.1–3.9) or Stage IV (AOR = 3.6; 95% CI 1.7–7.7) were independent predictors for the development of opportunistic infections.ConclusionThe prevalence of opportunistic infections among the HIV-infected patients who were in Pre-ART was higher than On-ART group. This finding reinforces the need for early initiation of ART for HIV-infected patients irrespective of their CD4 counts.

Short- and Long-term Risks of Highly Active Antiretroviral Treatment with Incident Opportunistic Infections among People Living with HIV/AIDS

Highly active antiretroviral therapy (HAART) causes a rapid increase of CD4 + T cells counts during the first 3–6 months of treatment and may enhance the development of opportunistic infections (OIs). However, the short- and long-term effects of HAART exposure on the development of incident OIs has not been extensively studied. This nationwide longitudinal study followed up a total of 26,258 people living with HIV/AIDS (PLWHA) to ascertain the short- and long-term effects of HAART on incident OIs. During 150,196 person-years of follow-up, 6,413 (24.4%) PLWHA had new onset of OIs. After adjusting for demographics, comorbidities, and AIDS status, PLWHA who received HAART were more likely to develop OIs than those who did not receive HAART. Considering the short- and long-term effects of HAART on the development of OIs, HAART was found to be a risk factor for developing OIs during the first 90 days of treatment, but a protective factor against OIs after 180 days of HAART use. The risk for the development of active OIs significantly decreased as the duration of HAART increased (P < 0.001). Our study suggests that HAART is a risk factor for developing OIs in the short term, but is a protective factor in the long term.

Pneumocystis Jirovecii Pneumonia after Initiation of Tofacitinib Therapy in Rheumatoid Arthritis: Case-Based Review.

The use of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) in rheumatic diseases is constantly increasing during the last decade. Tofacitinib is a new oral Janus Kinase (JAK) inhibitor, approved for rheumatoid arthritis (RA), psoriatic arthritis and ulcerative colitis. Safety data of tofacitinib derived from randomized controlled trials and long-term extension studies has demonstrated a moderate increase in the risk for common serious infections. We describe a case of Pneumocystis jirovecii pneumonia (PJP) in a woman on tofacitinib therapy for RA. Although tofacitinib use has been associated with the development of opportunistic infections, PJP has been rarely reported. PJP should be included in the differential diagnosis of patients with autoimmune disorders under newer oral JAK inhibitors therapy who present with fever, hypoxia and pulmonary infiltrates.

The role of cytomegalovirus in the development of opportunistic infections

The role of cytomegalovirus in the development of opportunistic infections

1571. Cost-Effectiveness Analysis of Duration of Valganciclovir Prophylaxis Among CMV Serology Mismatched (Donor+/Recipient−) Lung Transplant Recipients

BackgroundCytomegalovirus (CMV) is the most common cause of opportunistic infection (OI) following lung transplant (LTx), with incidence of 30–90%. CMV is associated with direct morbidity and indirect effects (e.g., graft failure, development of OIs and graft rejection (ACR), etc.), all of which lead to poor outcomes. Donor CMV positive, recipient negative (D+/R−) patients have the highest risk of CMV infections, for which they typically receive prolonged durations (≥1 year) of valganciclovir prophylaxis (Px). Px is limited by toxicity and ganciclovir-resistance. We performed a cost effectiveness analysis of differing lengths of Px in CMV D+/R− LTx patients.MethodsWe built a Markov state transition model using month-long cycles over a five-year time horizon, a 3% discount rate, and taking a healthcare system perspective. Model health states included episodes of CMV viremia and disease, ACR, and death. Identical hypothetical cohorts of D+/R− patients received 1–2 years of Px. Event probabilities were drawn from national data and local data from patients seen at our center. Cost data (Px and treatment, treatment of side effects, CMV-associated OI, viral load monitoring, etc.) were based on national estimates. Sensitivity analyses were performed on CMV infection incidence while on Px and time on Px.ResultsReceiving 1 and 2 years of Px had average total direct medical care costs of $115,182 and $141,290, respectively. The average life-years gained for receiving 2 years and 1 year of Px were 3.11 and 2.81, respectively, resulting in an incremental cost-effectiveness ratio (ICER) of $87,984 per life-year gained. A sensitivity analysis varying CMV infection incidence on Px showed that 1 year dominates 2 years of Px only when this incidence is >50% annually (i.e., 1 year of Px costs less and gains more life years). Real-world experience, however, shows that breakthrough CMV rate while on VGC Px is much <50% due to Px efficacy. If duration of Px is extended to 3 years, the ICER increases to $95,815/life-year (3.34 life-years gained) when compared with 1 year.ConclusionA longer duration of Px is predicted to lead to higher overall costs but increased life expectancy for CMV D+/R− mismatch Ltx patients. Px duration > 1 year for these patients may be economically reasonable.Disclosures C. J. Clancy, Merck: Grant Investigator, Research grant; Astellas: Grant Investigator, Research grant. M. H. Nguyen, Merck: Grant Investigator, Research grant; Astellas: Grant Investigator, Research grant.